HOMER1

Summary

HOMER1 (homer scaffold protein 1, HGNC:17512) is a protein-coding gene on chromosome 5q14.1, encoding Homer protein homolog 1 (Q86YM7). Postsynaptic density scaffolding protein.

This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function.

Source: NCBI Gene 9456 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_004272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17512
Approved symbol	HOMER1
Name	homer scaffold protein 1
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	Ves-1, SYN47, HOMER-1B
Ensembl gene	ENSG00000152413
Ensembl biotype	protein_coding
OMIM	604798
Entrez	9456

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000282260, ENST00000334082, ENST00000460741, ENST00000508576, ENST00000535690, ENST00000880231, ENST00000933296, ENST00000970825

RefSeq mRNA: 3 — MANE Select: NM_004272 NM_001277077, NM_001277078, NM_004272

CCDS: CCDS43335, CCDS64188, CCDS64189

Canonical transcript exons

ENST00000334082 — 9 exons

Exon	Start	End
ENSE00001005046	79447053	79447145
ENSE00001005053	79397527	79397637
ENSE00001005054	79450990	79451121
ENSE00001005056	79401899	79402055
ENSE00001161614	79439010	79439149
ENSE00001168577	79372636	79376197
ENSE00001386390	79456862	79457018
ENSE00001536880	79512770	79514134
ENSE00003583214	79396823	79396903

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4470 / max 1088.0057, expressed in 1636 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62271	8.0812	911
62269	2.8008	1034
62270	1.4786	757
62268	1.0791	580
62272	0.6843	381
62267	0.1774	69
62266	0.0765	38
62264	0.0432	13
62265	0.0258	10

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.51	gold quality
middle temporal gyrus	UBERON:0002771	98.38	gold quality
orbitofrontal cortex	UBERON:0004167	98.21	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.80	gold quality
endothelial cell	CL:0000115	97.78	gold quality
biceps brachii	UBERON:0001507	97.76	gold quality
choroid plexus epithelium	UBERON:0003911	96.60	gold quality
heart right ventricle	UBERON:0002080	96.58	gold quality
frontal pole	UBERON:0002795	96.44	gold quality
vastus lateralis	UBERON:0001379	96.40	gold quality
superior frontal gyrus	UBERON:0002661	96.31	gold quality
parietal lobe	UBERON:0001872	96.11	gold quality
postcentral gyrus	UBERON:0002581	95.92	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.78	gold quality
entorhinal cortex	UBERON:0002728	95.77	gold quality
quadriceps femoris	UBERON:0001377	95.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.76	gold quality
left ventricle myocardium	UBERON:0006566	94.63	gold quality
CA1 field of hippocampus	UBERON:0003881	93.82	gold quality
occipital lobe	UBERON:0002021	93.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.36	gold quality
cervix squamous epithelium	UBERON:0006922	93.26	gold quality
primary visual cortex	UBERON:0002436	93.17	gold quality
buccal mucosa cell	CL:0002336	93.04	gold quality
myocardium	UBERON:0002349	92.75	gold quality
skeletal muscle tissue	UBERON:0001134	92.53	gold quality
gluteal muscle	UBERON:0002000	92.39	gold quality
middle frontal gyrus	UBERON:0002702	91.90	gold quality
pigmented layer of retina	UBERON:0001782	91.66	gold quality
triceps brachii	UBERON:0001509	91.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.35
E-GEOD-124858	no	71.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

243 targeting HOMER1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762

Literature-anchored findings (GeneRIF, showing 38)

• HOMER1 was screened for an association with schizophrenia. (PMID:12815733)
• Polymorphism in the Homer1 gene is a potential risk factor for the development of cocaine dependence in an African American population. (PMID:16314758)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Data indicate that Homer1 plays a critical role in determining the apoptotic susceptibility to TRAIL. (PMID:19376111)
• study implicates the effects of allele A of the rs4704559 marker in susceptibility to psychotic symptoms in Parkinson disease (PMID:19648775)
• Haplotypes of the HOMER 1 and 2 genes are unlikely to play a major role in the pathophysiology of alcohol dependence. (PMID:20333726)
• This study reported significant associations between different polymorphisms of the HOMER 1 gene and psychopathology of schizophrenic patients at baseline and between HOMER 1 polymorphisms and therapy response after treatment with atypical antipsychotics. (PMID:20598711)
• HOMER1 plays a role in the etiology of major depression and genetic variation affects depression via the dysregulation of cognitive and motivational processes. (PMID:20673876)
• Homer dissociation from its targets evoked by the PPKKFR peptide led to Imin calcium channel activation but not to Imax calcium channel activation in A431 cells. (PMID:20926133)
• Homer1a transgene expression is transiently upregulated during increases in network activity and evokes agonist-independent signaling of group I metabotropic glutamate receptors that scales down expression of synaptic AMPA receptors. (PMID:21172614)
• monitored Homer1 and Homer2 expression and subcellular localization in skeletal muscle biopsies following 60 days of bedrest (PMID:21885651)
• HOMER1 encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, and is a novel autism-risk gene. (PMID:22558107)
• This review discusses the association of Homer 1 variants with the etiology of many neurological diseases, such as pain, mental retardation syndromes, Alzheimer’s disease, schizophrenia, addiction and traumatic brain injury. (PMID:22749857)
• Polymorphisms of DRD1, DLG4 and HOMER1 are associated with opiate abuse. (PMID:23044706)
• Overexpression of HOMER1A reduces neuropathic pain hypersensitivity. (PMID:23685007)
• The uncoupling of synaptic protein homer 1c from target proteins activates store-operated calcium entry in a neurotransmitter-like manner in human neuroblastoma cells. (PMID:23821062)
• data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects (PMID:24126708)
• Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of intrahepatic cholangiocarcinoma. (PMID:24815486)
• The mRNA levels of Homer1, IL-1beta, and TNF-alpha in coronary artery disease patients were significantly higher than those in the control group, but not Homer2 and Homer3. (PMID:25551602)
• these findings provide evidence for a new role of Homer1 supporting the regulation of Cav1.2 channels by STIM1. (PMID:25712868)
• The main focus of the present review is to offer an overview of the current knowledge about the potential role of Homer1a in depression and the signaling pathways responsible for Homer1a regulation. [review] (PMID:26641965)
• The present study was undertaken to determine the expression and functional significance of Homer1b/c in multiple myeloma (PMID:26718835)
• Study shows that Homer1b/c is constitutively expressed in astrocytes, where it clusters with mGlu5 and endoplasmic reticulum tubules to form sub-plasmalemmal microdomains; propose that Homer1a may represent one of the cellular mechanisms by which inflammatory astrocytic reactions are beneficial for limiting brain injury (PMID:27075036)
• Homer1 and Homer2 might be considered as novel diagnostic biomarkers for large-artery atherosclerosis stroke. (PMID:27832625)
• Resequencing three candidate genes (HOMER1, SLC6A4, and TEF) discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese. (PMID:27964944)
• This study demonstrate that altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. (PMID:28815330)
• Homer 1 rs7713917 gene variant associated with brain structure and function, severity of depression, and antidepressant response in patients affected by a major depressive episode in course of bipolar disorder. (PMID:29079138)
• Monomeric Homer 1a proteins increase activity of Imin channels, but did not modulate their electrophysiological properties. Recombinant Homer 1c protein did not block the induced calcium currents. (PMID:29923011)
• Study found the common variant rs7713917 in the HOMER1 gene to be significantly associated with suicide attempt in Chinese patient. (PMID:30219717)
• Homer1 regulates RyR1 by direct interaction. (PMID:31078268)
• Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression. (PMID:32142100)
• A single nucleotide polymorphism in the HOMER1 gene is associated with sleep latency and theta power in sleep electroencephalogram. (PMID:32645048)
• Multiple signaling pathways are essential for synapse formation induced by synaptic adhesion molecules. (PMID:33431662)
• The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells. (PMID:34204449)
• The Role of Stress-Induced Changes of Homer1 Expression in Stress Susceptibility. (PMID:34225586)
• Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome. (PMID:34788607)
• CircHOMER1 aggravates oxidative stress, inflammation and extracellular matrix deposition in high glucose-induced human mesangial cells. (PMID:36181383)
• Elaboration of the Homer1 recognition landscape reveals incomplete divergence of paralogous EVH1 domains. (PMID:38989636)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	homer1b	ENSDARG00000101759
mus_musculus	Homer1	ENSMUSG00000007617
rattus_norvegicus	Homer1	ENSRNOG00000047014

Paralogs (2): HOMER3 (ENSG00000051128), HOMER2 (ENSG00000103942)

Protein

Protein identifiers

Homer protein homolog 1 — Q86YM7 (reviewed: Q86YM7)

All UniProt accessions (2): Q86YM7, Q86YM6

UniProt curated annotations — full annotation on UniProt →

Function. Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoform 1 regulates the trafficking and surface expression of GRM5. Isoform 3 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1 to regulate synaptic metabotropic glutamate function. Isoform 3, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development. Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines. Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA.

Subunit / interactions. Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines. Interacts with GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2 and SHANK3. Interacts with IFT57 and OPHN1. Isoform 1 encodes a coiled-coil structure that mediates homo- and heteromultimerization. Interacts with SHANK1; forms high-order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent. Interacts with NFATC4. Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA. Interacts with SRGAP2.

Subcellular location. Cytoplasm. Postsynaptic density. Synapse. Cell projection. Dendritic spine.

Domain organisation. The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement.

Similarity. Belongs to the Homer family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86YM7-1	1, 1b	yes
Q86YM7-2	2, 1e
Q86YM7-3	3, 1h

RefSeq proteins (3): NP_001264006, NP_001264007, NP_004263* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000697	WH1/EVH1_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR044100	Homer_EVH1	Domain
IPR045027	Homer	Family

Pfam: PF00568

UniProt features (13 total): splice variant 3, region of interest 2, compositionally biased region 2, modified residue 2, initiator methionine 1, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YM7-F1	87.47	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 306

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 427 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_ADULT_BEHAVIOR, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, TATTATA_MIR374, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (14): skeletal muscle contraction (GO:0003009), phospholipase C-activating G protein-coupled glutamate receptor signaling pathway (GO:0007206), G protein-coupled glutamate receptor signaling pathway (GO:0007216), chemical synaptic transmission (GO:0007268), positive regulation of signal transduction (GO:0009967), behavioral response to cocaine (GO:0048148), skeletal muscle fiber development (GO:0048741), protein tetramerization (GO:0051262), response to calcium ion (GO:0051592), positive regulation of calcium ion transport (GO:0051928), regulation of synaptic transmission, glutamatergic (GO:0051966), regulation of calcium ion import (GO:0090279), regulation of dendritic spine maintenance (GO:1902950), regulation of store-operated calcium entry (GO:2001256)

GO Molecular Function (4): G protein-coupled glutamate receptor binding (GO:0035256), signaling adaptor activity (GO:0035591), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (18): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), Z disc (GO:0030018), axon (GO:0030424), dendrite (GO:0030425), costamere (GO:0043034), dendritic spine (GO:0043197), neuron spine (GO:0044309), apical part of cell (GO:0045177), glutamatergic synapse (GO:0098978), postsynaptic cytosol (GO:0099524), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
regulation of calcium ion transport	3
neuron projection	3
postsynapse	2
synapse	2
striated muscle contraction	1
musculoskeletal movement	1
PLC activating G protein-coupled glutamate receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
G protein-coupled receptor signaling pathway	1
glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor activity	1
anterograde trans-synaptic signaling	1
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
adult behavior	1
response to cocaine	1
skeletal muscle tissue development	1
myotube cell development	1
protein complex oligomerization	1
response to metal ion	1
calcium ion transport	1
positive regulation of monoatomic ion transport	1
synaptic transmission, glutamatergic	1
modulation of chemical synaptic transmission	1
calcium ion import	1
dendritic spine maintenance	1
regulation of postsynapse organization	1
regulation of plasma membrane bounded cell projection organization	1
store-operated calcium entry	1
G protein-coupled receptor binding	1
glutamate receptor binding	1
protein-macromolecule adaptor activity	1
protein binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOMER1	GRM5	P41594	999
HOMER1	DLG4	P78352	977
HOMER1	DLGAP1	P78335	972
HOMER1	GRM1	Q13255	971
HOMER1	SHANK1	Q9Y566	950
HOMER1	ITPR1	Q14643	941
HOMER1	SHANK3	Q9BYB0	886
HOMER1	GRIA1	P42261	873
HOMER1	ITPR3	Q14573	865
HOMER1	SHANK2	Q9UPX8	852
HOMER1	SYP	P08247	837
HOMER1	TRPC1	P48995	834
HOMER1	DNM3	Q9UQ16	801
HOMER1	SLC17A7	Q9P2U7	800
HOMER1	HCLS1	P14317	798

IntAct

175 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
HOMER1	HOMER3	psi-mi:“MI:0915”(physical association)	0.870
HOMER3	HOMER1	psi-mi:“MI:0915”(physical association)	0.870
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
SARG	HOMER1	psi-mi:“MI:0915”(physical association)	0.780
HOMER1	SARG	psi-mi:“MI:0915”(physical association)	0.780
HOMER1	TRAF5	psi-mi:“MI:0914”(association)	0.740
HOMER1	ABI3	psi-mi:“MI:0915”(physical association)	0.740
TRAF5	HOMER1	psi-mi:“MI:0915”(physical association)	0.740
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
ABI3	HOMER1	psi-mi:“MI:0915”(physical association)	0.740
FRYL	YWHAZ	psi-mi:“MI:0914”(association)	0.710
CENPQ	HOMER1	psi-mi:“MI:0915”(physical association)	0.700
NUP54	HOMER1	psi-mi:“MI:0915”(physical association)	0.670
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640

BioGRID (166): HOMER1 (Two-hybrid), C1orf116 (Two-hybrid), C19orf57 (Two-hybrid), HOMER1 (Affinity Capture-MS), HOMER1 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER3 (Affinity Capture-MS), ACTB (Affinity Capture-MS), SPTBN4 (Affinity Capture-MS), KIF5C (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), TRAF5 (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), HOMER1 (Affinity Capture-MS)

ESM2 similar proteins: A8WUP2, C5DY19, E9Q7G0, O42184, O55156, P13496, P30622, P34562, P45970, P61430, Q06704, Q11102, Q13439, Q14203, Q15643, Q2KJ56, Q2KN97, Q2KN99, Q2KNA0, Q2KNA1, Q5M775, Q5SXY1, Q5U312, Q5U4E6, Q66H89, Q69YQ0, Q6PCJ1, Q75AF5, Q7FAD5, Q86YM7, Q8CGB3, Q8HYY4, Q8MSS1, Q8S2T0, Q90631, Q91VW5, Q922J3, Q9BZF9, Q9D5R3, Q9EP71

Diamond homologs: O88801, Q2KJ56, Q86YM7, Q99JP6, Q9NSB8, Q9NSC5, Q9QWW1, Q9Z214, Q9Z2X5, Q9Z2Y3, Q5TJ65, P50551, P70460, Q2TA49

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HOMER1	“up-regulates activity”	SHANK1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPase Effectors	9	7.5×	1e-03
Cell Cycle	11	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1996 predictions. Top by Δscore:

Variant	Effect	Δscore
5:79376201:C:CT	acceptor_gain	1.0000
5:79376202:A:T	acceptor_gain	1.0000
5:79396817:GCTCA:G	donor_loss	1.0000
5:79396818:CTCA:C	donor_loss	1.0000
5:79396819:TCAC:T	donor_loss	1.0000
5:79396820:CA:C	donor_loss	1.0000
5:79396821:ACCT:A	donor_loss	1.0000
5:79396822:C:A	donor_loss	1.0000
5:79396904:C:CA	acceptor_loss	1.0000
5:79396904:C:CC	acceptor_gain	1.0000
5:79397522:AATAC:A	donor_loss	1.0000
5:79397524:TA:T	donor_loss	1.0000
5:79397525:A:AC	donor_gain	1.0000
5:79397525:ACCTC:A	donor_loss	1.0000
5:79397526:C:CC	donor_gain	1.0000
5:79397526:CCT:C	donor_gain	1.0000
5:79397528:T:TA	donor_gain	1.0000
5:79397531:T:TA	donor_gain	1.0000
5:79397633:GTCAC:G	acceptor_gain	1.0000
5:79397634:TCAC:T	acceptor_gain	1.0000
5:79397635:CAC:C	acceptor_gain	1.0000
5:79397635:CACC:C	acceptor_gain	1.0000
5:79397636:AC:A	acceptor_gain	1.0000
5:79397637:CC:C	acceptor_gain	1.0000
5:79397638:C:CC	acceptor_gain	1.0000
5:79397932:T:TA	donor_gain	1.0000
5:79401894:ATTAC:A	donor_loss	1.0000
5:79401895:TTA:T	donor_loss	1.0000
5:79401896:TA:T	donor_loss	1.0000
5:79401897:A:C	donor_loss	1.0000

AlphaMissense

2332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:79401952:A:G	W211R	1.000
5:79401952:A:T	W211R	1.000
5:79401973:A:G	S204P	1.000
5:79401981:A:G	L201P	1.000
5:79401993:A:G	L197P	1.000
5:79401993:A:T	L197H	1.000
5:79402014:A:G	L190P	1.000
5:79447111:G:T	A110D	1.000
5:79447131:A:C	F103L	1.000
5:79447131:A:T	F103L	1.000
5:79447132:A:G	F103S	1.000
5:79447133:A:G	F103L	1.000
5:79447143:A:C	F99L	1.000
5:79447143:A:T	F99L	1.000
5:79447144:A:G	F99S	1.000
5:79447145:A:G	F99L	1.000
5:79450997:A:G	L96P	1.000
5:79451014:G:C	F90L	1.000
5:79451014:G:T	F90L	1.000
5:79451015:A:C	F90C	1.000
5:79451015:A:G	F90S	1.000
5:79451016:A:G	F90L	1.000
5:79451018:C:A	G89V	1.000
5:79451018:C:T	G89E	1.000
5:79451019:C:G	G89R	1.000
5:79451019:C:T	G89R	1.000
5:79451021:A:C	L88W	1.000
5:79451021:A:G	L88S	1.000
5:79451024:C:A	G87V	1.000
5:79451024:C:T	G87E	1.000

dbSNP variants (sampled 300 via entrez): RS1000013082 (5:79387305 T>C), RS1000074143 (5:79380648 C>A,G), RS1000084729 (5:79388628 A>G), RS1000087037 (5:79478434 A>G), RS1000112759 (5:79460172 A>G), RS1000120879 (5:79373584 T>C), RS1000123374 (5:79469732 A>G), RS1000129867 (5:79392341 A>G), RS1000169948 (5:79497312 AAAAGATTAGAG>A), RS1000257693 (5:79489401 G>C), RS1000266570 (5:79422932 C>A), RS1000294093 (5:79373428 A>G), RS1000300494 (5:79399397 G>A,T), RS1000333912 (5:79483287 T>C,G), RS1000349971 (5:79476461 C>G)

Disease associations

OMIM: gene MIM:604798 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000136_4	Height	3.000000e-06
GCST000743_2	Major depressive disorder	1.000000e-06
GCST002670_3	Blood and toenail selenium levels	4.000000e-12
GCST002671_7	Toenail selenium levels	1.000000e-07
GCST003944_29	Hepcidin/ferritin ratio	6.000000e-06
GCST008103_152	Bipolar disorder	5.000000e-06
GCST009218_8	Lateral ventricle temporal horn volume	2.000000e-06
GCST009391_176	Metabolite levels	4.000000e-06
GCST011681_5	Cryptococcosis in HIV infection	7.000000e-06
GCST012465_20	Bipolar disorder	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio
EFO:0010476	dimethylglycine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4704559	Toxicity	3	levodopa	Parkinson Disease

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4704559	HOMER1	3	4.50	1	levodopa
rs4704560	HOMER1		0.00	0
rs10942981	HOMER1		0.00	0

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cocaine	increases response to substance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Levodopa	affects response to substance	1
Manganese	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.